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Trial record 11 of 15 for:    Hydrochlorothiazide AND metoprolol succinate

The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial (AVEC)

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ClinicalTrials.gov Identifier: NCT00605072
Recruitment Status : Completed
First Posted : January 30, 2008
Results First Posted : February 15, 2013
Last Update Posted : February 15, 2013
Sponsor:
Collaborators:
National Institute on Aging (NIA)
Hebrew SeniorLife
Information provided by (Responsible Party):
Ihab Hajjar, University of Southern California

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Cognitive Impairment
Hypertension
Aging
Interventions Drug: candesartan
Drug: lisinopril
Drug: hydrochlorothiazide
Drug: nifedipine, long acting
Drug: metoprolol, long-acting
Enrollment 53
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Lisinopril Candesartan HCTZ
Hide Arm/Group Description

Angiotensin-Converting Enzyme (ACE) Inhibitor: lisinopril : orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Period Title: Overall Study
Started 18 20 15
Completed 11 9 11
Not Completed 7 11 4
Arm/Group Title ACEI (Lisinopril) ARB (Candesartan) HCTZ Total
Hide Arm/Group Description

Angiotensin-Converting Enzyme (ACE) Inhibitor: lisinopril : orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Total of all reporting groups
Overall Number of Baseline Participants 18 20 15 53
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 20 participants 15 participants 53 participants
71  (7) 71  (9) 71  (7) 71  (7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 20 participants 15 participants 53 participants
Female
11
  61.1%
11
  55.0%
9
  60.0%
31
  58.5%
Male
7
  38.9%
9
  45.0%
6
  40.0%
22
  41.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 18 participants 20 participants 15 participants 53 participants
18 20 15 53
1.Primary Outcome
Title Cognitive Assessment: Trail Making Test Part B
Hide Description This test requires the connection of sequentially numbered circles (A), and the connection of circles marked by numbers and letters in alternating sequence (B). This test is considered a benchmark of executive function. The test score is the time required to complete the task in seconds.
Time Frame Baseline-12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ACEI (Lisinopril) ARB (Candesartan) HCTZ
Hide Arm/Group Description:

Angiotensin-Converting Enzyme (ACE) Inhibitor: lisinopril : orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Overall Number of Participants Analyzed 18 20 15
Least Squares Mean (Standard Error)
Unit of Measure: seconds
-14  (9) 17  (10) 4  (9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACEI (Lisinopril), ARB (Candesartan), HCTZ
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments p-value for between group comparison (group*visit)
Method Mixed Models Analysis
Comments Adjusted for baseline AGE and Mini-Mental-State-Examination
2.Primary Outcome
Title Cognitive Assessment: Hopkins Verbal Learning- Immediate Recall
Hide Description This is a 12-item list learning test in which individuals are presented three learning and recall trials followed by a delayed recall and 24 item recognition test. The HVLT-R has been identified as an ideal memory measure for elderly patients, and appropriate reliability and validity have been shown in older individuals. The test score is the number of correct answers in the delayed recall ( score range 0-12)
Time Frame Baseline-12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ACEI (Lisinopril) ARB (Candesartan) HCTZ
Hide Arm/Group Description:

Angiotensin-Converting Enzyme (ACE) Inhibitor: lisinopril : orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Overall Number of Participants Analyzed 18 20 15
Least Squares Mean (Standard Error)
Unit of Measure: number words remembered
-1  (1) -2  (1) -3  (1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACEI (Lisinopril), ARB (Candesartan), HCTZ
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.87
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
3.Primary Outcome
Title Cognitive Assessment: Forward Digit Span Test
Hide Description This test consists of series of digits of increasing length, some of which are recited as presented, and some of which are to be recited in reversed order. The forward digit span score ranges from 0 (ie cannot repeat two digits) to 8 ( participant can repeat up to 8 digits)
Time Frame Baseline-12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ACEI (Lisinopril) ARB (Candesartan) HCTZ
Hide Arm/Group Description:

Angiotensin-Converting Enzyme (ACE) Inhibitor: lisinopril : orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Overall Number of Participants Analyzed 18 20 15
Least Squares Mean (Standard Error)
Unit of Measure: number of digits repeated
-0.3  (0.3) 0.02  (0.04) -0.04  (0.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACEI (Lisinopril), ARB (Candesartan), HCTZ
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.79
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
4.Secondary Outcome
Title Blood Pressure Outcome: Systolic BP
Hide Description Blood pressure was measured as follows: the participant was in the sitting position, rested for 5 minutes, no caffeine or smoking 2 hours prior to measurement, using appropriate cuff size (covering 60% of upper arm length and 80% of arm circumference), correct cuff placement (1-2 inches above brachial pulse on bare arm), and the bell of the stethoscope. The systolic blood pressure was defined as the pressure corresponding to the first korotkoff sounds (K1) and the diastolic as the pressure corresponding to the last korotkoff sound (K5). Blood pressure was measured in both arms and recorded
Time Frame Baseline-12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ACEI (Lisinopril) ARB (Candesartan) HCTZ
Hide Arm/Group Description:

Angiotensin-Converting Enzyme (ACE) Inhibitor: lisinopril : orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Overall Number of Participants Analyzed 17 17 13
Least Squares Mean (Standard Error)
Unit of Measure: mm Hg
28  (5) 27  (5) 21  (5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACEI (Lisinopril), ARB (Candesartan), HCTZ
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.74
Comments [Not Specified]
Method Mixed Models Analysis
Comments adjusted for age
5.Secondary Outcome
Title Blood Flow Velocity, Sitting
Hide Description This reports the change in the least square mean from baseline to 12 months, adjusted for age
Time Frame Baseline-12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ACEI (Lisinopril) ARB (Candesartan) HCTZ
Hide Arm/Group Description:

Angiotensin-Converting Enzyme (ACE) Inhibitor: lisinopril : orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Overall Number of Participants Analyzed 17 17 13
Least Squares Mean (Standard Error)
Unit of Measure: cm/sec
-0.3  (1.5) -2.85  (1.71) 0.35  (1.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACEI (Lisinopril), ARB (Candesartan), HCTZ
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted for age at baseline
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ACEI (Lisinopril) ARB (Candesartan) HCTZ
Hide Arm/Group Description

Angiotensin-Converting Enzyme (ACE) Inhibitor: lisinopril : orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months

nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

All-Cause Mortality
ACEI (Lisinopril) ARB (Candesartan) HCTZ
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
ACEI (Lisinopril) ARB (Candesartan) HCTZ
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)   0/20 (0.00%)   0/15 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
ACEI (Lisinopril) ARB (Candesartan) HCTZ
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/18 (27.78%)   6/20 (30.00%)   06/15 (40.00%) 
Injury, poisoning and procedural complications       
Hospitalization (non-elective)  4/18 (22.22%)  3/20 (15.00%)  3/15 (20.00%) 
Nervous system disorders       
Dizziness   5/18 (27.78%)  6/20 (30.00%)  6/15 (40.00%) 
Weakness or Fatigue  3/18 (16.67%)  1/20 (5.00%)  1/15 (6.67%) 
Fall, non-injurious  4/18 (22.22%)  1/20 (5.00%)  2/15 (13.33%) 
Respiratory, thoracic and mediastinal disorders       
Cough  5/18 (27.78%)  4/20 (20.00%)  3/15 (20.00%) 
Indicates events were collected by systematic assessment
The main limitation is the small sample size. The validity of TCD measurements as an index of cerebral blood flow is based on the assumption that cerebral vessel diameters are constant but we didn't have brain imaging to validate this assumption.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Ihab Hajjar
Organization: University of Southern California
Phone: 323-226-6720
Responsible Party: Ihab Hajjar, University of Southern California
ClinicalTrials.gov Identifier: NCT00605072     History of Changes
Other Study ID Numbers: IA0127
K23AG030057 ( U.S. NIH Grant/Contract )
First Submitted: January 11, 2008
First Posted: January 30, 2008
Results First Submitted: December 4, 2012
Results First Posted: February 15, 2013
Last Update Posted: February 15, 2013